Plasma Endocannabinoid Alterations in Individuals with Substance Use Disorder are Dependent on the “Mirror Effect” of Schizophrenia

Abstract

Schizophrenia is a complex psychiatric disorder strongly associated with substance use disorders. Theoretically, schizophrenia and SUD may share endocannabinoid alterations in the brain reward system. The main endocannabinoids, anandamide, and 2-arachidonoylglycerol, are lipids which bind cannabinoid receptors. Oleoylethanolamide (OEA), a fatty-acid ethanolamide, binds peroxisome proliferator-activated receptors. The endocannabinoid system has been shown to be impaired in schizophrenia, and recently, our group has shown that schizophrenia patients with SUD have elevated peripheral levels of anandamide and OEA that do not normalize after 3-month treatment with quetiapine. Objective For comparative purposes, we aimed to measure endocannabinoids in non-psychosis substance abusers and non-abusing schizophrenia patients. Methods Using liquid chromatography and mass spectrometry, we measured plasma levels of anandamide and OEA in non-psychosis SUD patients, non-abusing schizophrenia patients, and healthy controls. In an open-label manner, all patients received 12-week treatment with quetiapine. Results Anandamide and OEA were reduced in substance abusers without schizophrenia, relative to healthy controls (p < 0.05). Both endocannabinoids were unchanged in non-abusing schizophrenia patients. After quetiapine, anandamide, and OEA levels remained significantly reduced the SUD group (p < 0.05). Discussion Taken together with results of our previous study performed in dual-diagnosis patients, our results suggest that peripheral anandamide and OEA levels are impaired in patients with SUD in opposite ways according to the presence or absence of schizophrenia. Endocannabinoid alterations did not change with treatment, suggesting that they are trait markers. Further studies are necessary to understand the role of endocannabinoids in substance abusers with and without schizophrenia and to examine therapeutic implications.

Circulating Endocannabinoids: From Whence Do They Come and Where are They Going?

“…These findings suggest the hypothesis that elevation of CSF AEA reflects a beneficial recruitment of CNS AEA signaling. No differences in circulating AEA were detected between schizophrenics and controls in which robust differences in CSF concentrations were found (Leweke et al, 2007) and in another study (Desfosses et al, 2012). However, other studies have found increased circulating AEA concentrations in schizophrenics compared to controls (De Marchi et al, 2003;Potvin et al, 2008).…”

Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity

“…; Desfosses et al . ). Further studies have been conducted to determine circulating eCB levels in alcohol users (Mangieri et al .…”

“…; Desfosses et al . ). However, there is a low number of studies concerning plasma eCB and their congeners in individuals with substance use disorders (Potvin et al .…”

Sex Differences in Psychiatric Comorbidity and Plasma Biomarkers for Cocaine Addiction in Abstinent Cocaine-Addicted Subjects in Outpatient Settings

“…Several lines of evidence suggest that bioactive lipids, such as endocannabinoids and related congeners, are involved in the acquisition and maintenance of drug-taking behavior and other processes associated with addiction ( 38 , 39 ). However, all of these studies are based on preclinical observations because there are few studies concerning plasma lipid derivatives in individuals with substance use disorders ( 40 , 41 ), principally with alcohol use ( 42 , 43 ). Endocannabinoids act on cannabinoid receptors to exert their effects and are composed of two structural types of lipid derivatives: N -acyl-ethanolamines (e.g., AEA) and 2-acyl-glycerols (e.g., 2-AG).…”